Development of Shortened miR-506-3p Mimics Exhibiting Strong Differentiation-Inducing Activity in Neuroblastoma Cells.

microRNA mimics are synthetic RNA molecules that imitate the mature miRNA duplexes and their functions. These mimics have shown promise in treating cancers. Nucleotide chemical modifications of microRNA mimics have been investigated and have improved the stability of miRNA mimics. However, the potential therapeutic benefit of mimic analogs based on sequence modifications has not been explored. miR-506-3p was identified as a differentiation-inducing microRNA in neuroblastoma cells, suggesting the potential of applying the miR-506-3p mimic in neuroblastoma differentiation therapy. In this study, we explored the possibility of developing shortened miR-506-3p analogs that can maintain differentiation-inducing activities comparable to the wild-type miR-506-3p mimic. We found that deleting up to two nucleotides at either the 3' end or within the middle region of the miR-506-3p sequence fully maintained the differentiation-inducing activity when compared to the wild-type mimic. Deleting up to four nucleotides from the 3' end or deleting three nucleotides in the middle positions diminished the differentiation-inducing activity, but the analogs still maintained differentiation-inducing activities that were significantly higher than the negative control oligo. The shortened analog designs potentially benefit patients from two perspectives: (1) the reduced cost of manufacturing shortened analogs, and (2) the reduced non-specific toxicity due to their smaller molecular sizes.

Intravascular US-Guided Portal Vein Access: Improved Procedural Metrics during TIPS Creation.

PURPOSE: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) outcomes and procedure metrics with the use of three different image guidance techniques for portal vein (PV) access during TIPS creation. MATERIALS AND METHODS: A retrospective review of consecutive patients who underwent TIPS procedures for a range of indications during a 28-month study period identified a population of 68 patients. This was stratified by PV access techniques: fluoroscopic guidance with or without portography (n = 26), PV marker wire guidance (n = 18), or intravascular ultrasound (US) guidance (n = 24). Procedural outcomes and procedural metrics, including radiation exposure, contrast agent volume used, procedure duration, and PV access time, were analyzed. RESULTS: No differences in demographic or procedural characteristics were found among the three groups. Technical success, technical success of the primary planned approach, hemodynamic success, portosystemic gradient, and procedure-related complications were not significantly different among groups. Fluoroscopy time (P = .003), air kerma (P = .01), contrast agent volume (P = .003), and total procedural time (P = .02) were reduced with intravascular US guidance compared with fluoroscopic guidance. Fluoroscopy time (P = .01) and contrast agent volume (P = .02) were reduced with intravascular US guidance compared with marker wire guidance. CONCLUSIONS: Intravascular US guidance of PV access during TIPS creation not only facilitates successful TIPS creation in patients with challenging anatomy, as suggested by previous investigations, but also reduces important procedure metrics including radiation exposure, contrast agent volume, and overall procedure duration compared with fluoroscopically guided TIPS creation.

Risk of hernia incarceration following transjugular intrahepatic portosystemic shunt placement.

PURPOSE: Hernia complications after creation of a transjugular intrahepatic portosystemic shunt (TIPS) have been reported, although the incidence of this complication is unknown. This study was designed to determine the incidence, morbidity, and outcome of hernia complications in patients with preexisting abdominal or inguinal hernias after TIPS creation. MATERIALS AND METHODS: The medical records of 244 consecutive patients undergoing TIPS creation between 1999 and 2007 at a single institution were reviewed. The study population was 57 patients (23%) with a preprocedural abdominal or inguinal hernia. The investigated outcome was small bowel obstruction or postprocedural incarceration of a preexisting hernia. Demographic and procedural variables were evaluated for an associated increased risk of hernia complications. RESULTS: Hernia complications developed in 25% of patients (14 of 57) after TIPS creation at a mean presentation of 62 days (range, 2-588 d). Thirteen complications (93%) required emergent surgery, of which four (29%) required bowel resection for necrosis. There were no resulting deaths. Ninety-eight percent of patients with a hernia complication had the procedure to treat refractory ascites. The indication of refractory ascites was significantly associated with the risk of a hernia complication (P = .002). CONCLUSIONS: A 25% incidence of hernia complications following TIPS creation in patients being treated for refractory ascites is higher than expected; emergent surgery is required in most cases. Further investigation to formulate a plan for elective management is warranted.

Metaanalysis of survival, complications, and imaging response following chemotherapy-based transarterial therapy in patients with unresectable intrahepatic cholangiocarcinoma.

PURPOSE: Unresectable intrahepatic cholangiocarcinoma represents a devastating illness with poor outcomes when treated with standard systemic therapies. Several smaller nonrandomized outcomes studies have been reported for such patients undergoing transarterial therapies. A metaanalysis was performed to assess primary clinical and imaging outcomes, as well as complication rates, following transarterial interventions in this patient population. MATERIALS AND METHODS: By using standard search techniques and metaanalysis methodology, published reports (published in 2012 and before) evaluating survival, complications, and imaging response following transarterial treatments for patients with unresectable intrahepatic cholangiocarcinoma were identified and evaluated. RESULTS: A total of 16 articles (N = 542 subjects) met the inclusion criteria and are included. Overall survival times were 15.7 months ± 5.8 and 13.4 months ± 6.7 from the time of diagnosis and time of first treatment, respectively. The overall weighted 1-year survival rate was 58.0% ± 14.5. More than three fourths of all subjects (76.8%) exhibited a response or stable disease on postprocedure imaging; 18.9% of all subjects experienced severe toxicities (National Cancer Institute/World Health Organization grade ≥ 3), and most experienced some form of postembolization syndrome. Overall 30-day mortality rate was 0.7%. CONCLUSIONS: As demonstrated by this metaanalysis, transarterial chemotherapy-based treatments for cholangiocarcinoma appears to confer a survival benefit of 2-7 months compared with systemic therapies, demonstrate a favorable response by imaging criteria, and have an acceptable postprocedural complication profile. Such therapies should be strongly considered in the treatment of patients with this devastating illness.

Skin Necrosis Resulting from Nontarget Embolization of the Falciform Artery during Transarterial Chemoembolization with Drug-Eluting Beads.

Intra-arterial embolic therapies are a mainstay of liver-directed therapies to palliate symptoms, improve survival, and bridge patients to transplantation. Vascular anatomy and type of embolic used can lead to complications of nontarget embolization with varying clinical consequences. This case report describes a rare, nontarget embolization of the falciform artery leading to supraumbilical skin necrosis.

Endovascular therapies for primary postpartum hemorrhage: techniques and outcomes.

Interventional radiologists are often consulted for acute management of hemorrhagic complications in obstetric and gynecologic patients. The aim of this article is to review the common indications for vascular embolization in obstetric and gynecologic emergencies, specifically in the setting of primary postpartum hemorrhage, and to discuss the technique and outcomes of endovascular treatment.

Pelvic vascular malformations.

Vascular malformations (VMs) comprise a wide spectrum of lesions that are classified by content and flow characteristics. These lesions, occurring in both focal and diffuse forms, can involve any organ and tissue plane and can cause significant morbidity in both children and adults. Since treatment strategy depends on the type of malformation, correct diagnosis and classification of a vascular lesion are crucial. Slow-flow VMs (venous and lymphatic malformations) are often treated by sclerotherapy, whereas fast-flow lesions (arteriovenous malformations) are generally managed with embolization. In addition, some cases of VMs are best treated surgically. This review will present an overview of VMs in the female pelvis as well as a discussion of endovascular therapeutic techniques.

The treatment of primary and metastatic hepatic neoplasms using percutaneous cryotherapy.

Cryotherapy has been used clinically in the treatment of metastatic liver malignancies since the 1980s. Rapid freezing to sub-zero temperatures promotes ice formation in the extracellular space and the exit of intracellular water. Cellular death is the result of dehydration, protein denaturation, and microcirculatory failure. Cryotherapy probes use nitrogen or argon gas as a coolant and the development of the ice ball can be monitored using ultrasound, computed tomography, or magnetic resonance imaging. Traditionally, cryotherapy has been performed during laparoscopy or laparotomy, using intraoperative ultrasound for image guidance. A decrease in cryoprobe size (from ~24 Fr to ~15 gauge) in conjunction with experience gained in open cryosurgical treatment has allowed the development of minimally invasive percutaneous approaches. In this review, we describe the use of cryotherapy for treatment of primary or secondary liver neoplasms using a percutaneous approach.